Many important drugs, particularly anticancer agents, are hydrophobic compounds which are sparingly soluble in water. In order to achieve desired therapeutic effects using such drugs, it is usually required that the drugs be solubilized for administration to patients. Thus, the solubilization of a sparingly water-soluble anticancer agent represents an important technique for making a formulation thereof for oral or parenteral use, particularly for producing a formulation for use in intravenous administration.
One method for solubilizing a sparingly water-soluble anticancer agent is addition of a surfactant. By way of example, a polyoxyethylene castor oil derivative (Cremophor) is used to solubilize paclitaxel. Other methods for solubilizing a sparingly water-soluble anticancer agent include use of a micelle-forming block copolymer as a carrier for the agent, described, for example, in Japanese Patent Application Laying Open (KOKAI) Nos. 6-107565, 6-206815, and 11-335267, and the like, and formation of an included paclitaxel-containing micelle using poly(ethylene oxide)-poly(β-benzylaspartate-co-aspartic acid) block copolymer, described in Japanese Patent Application Laying Open (KOKAI) No. 2001-226294.
However, the solubilization method using a surfactant shows harmful side effects such as hypersensitive reaction due to the surfactant, and also has the problem that, because of low stability of the preparation, agent precipitation occurs when the solution is stored, or allowed to stand for a long period of time.
In addition, intravenous administration of a pharmaceutical preparation using a block copolymer as a carrier for a sparingly water-soluble anticancer agent, e.g. a taxane anticancer agent, has not achieved that it maintains a higher concentration of the agent relative to administration of the agent alone and leads to enhanced pharmacological effects of the agent and reduced side effects thereof.
Thus, there has been a need for a pharmaceutical preparation which enhances the solubility of a sparingly water-soluble anticancer agent in water, which maintains an increased concentration of the agent, and yields enhanced pharmacological effects of the agent and reduced side effects thereof.